As replication in indepen- dent samples is a key attribute of genetic associations, we have re-examined the reported association by genotyping these. (TAA)n ...
brief communications © 2001 Nature Publishing Group http://genetics.nature.com
© 2001 Nature Publishing Group http://genetics.nature.com
Acknowledgments
We thank the patients and families for participation and Y.-M. Lim for technical assistance. This study was funded by a research grant from Bristol-Myers Squibb, Millennium Pharmaceuticals and Affymetrix (E.S.L.); the Medical Research Council (UK), the Wellcome Trust, and the Jansen Research Foundation (M.J.O., M.C.O. and G.K.); the German Israeli Foundation for Scientific Research (D.B.W. and B.L.); and Deutsche Forschungsgemeinschaft (SFB400) (W.M. and D.B.W.). Received 30 November 2000; accepted 4 April 2001.
Pamela Sklar1,2,3, Sibylle G. Schwab4, Nigel M. Williams5, Mark Daly3, Stephen Schaffner3, Wolfgang Maier6, Margot Albus 7, Matyas Trixler8, Peter Eichhammer9, Bernard Lerer10, Joachim
Hallmayer11, Nadine Norton5, Hywel Williams5, Stan Zammit5, Alastair G. Cardno5, Sue Jones5, Geraldine McCarthy5, Vihra Milanova12, George Kirov5, Michael C. O’Donovan5, Eric S. Lander3, Michael J. Owen5 & Dieter B. Wildenauer4 1Department
of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. 2Harvard Medical School, Boston, Massachusetts, 02115 USA. 3Whitehead Institute/MIT Center for Genome Research, One Kendall Square, Building 300, Cambridge, Massachusetts,02139 USA. 4Molecular Genetics Laboratory, Department of Psychiatry, University of Bonn, D-53111 Bonn, Germany. 5Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK. 6Department of Psychiatry, University of Bonn, D-53105 Bonn,
Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland The NOTCH4 gene was recently reported to be associated with schizophrenia1 based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.
A reported association between susceptibility to schizophrenia and NOTCH4 by Wei and Hemmings1 is based on excess transmission of NOTCH4 alleles from heterozygous parents to schizophrenic offspring in 80 trios of British descent. As determined by analysis with the transmission disequilibrium test2 (TDT), the strongest evidence derived from a (TAA)n microsatellite, approximately 10 kb upstream of NOTCH4 (P
